Inhibiting agents of tissue factor (TF) are useful as inhibitors of blood coagulation, inhibitors of angiogenesis, therapeutic agents for arteriosclerosis, and the like. However, inhibiting agents of human tissue factor are highly species-specific, and, for example, anti-human TF antibody does not react to tissue factors from animals other than primates. Therefore, the creation of animals that express human TF is highly desired for the evaluation of inhibiting agents of human TF.
Though a knock-out mouse for human TF exhibits embryonic lethality, the expression of human TF can circumvent embryonic lethality (Parry G C N et al., J. Clin. Invest. 101:560-569 (1998)). However, as this mouse has an introduced human TF minigene, the expression of tissue factor is low and thus breeding performance is poor (Erlich J. et al., Proc. Natl. Acad. Sci. USA 96:8138-8143 (1999)).